As part of The Renal Working Group of the Cardiovascular Health Study (CHS), we have shown that levels of kidney function, as ascertained by serum creatinine, are associated with inflammatory markers as well as clinical and subclinical cardiovascular disease (CVD). We have recently also measured cystatin-C, a more sensitive and novel measure of kidney function. This has allowed a major breakthrough in our understanding of the extent to which kidney function impacts age-related health. Whereas serum creatinine evels only detect a small subset of elderly individuals with the most impaired kidney function, cystatin-C appears to have a linear association with several aging risk factors, as well as subclinical and clinical CVD. These findings suggest that kidney function may play a central role in determining aging success. This proposal is a longitudinal assessment of kidney function, as measured by cystatin-C, and its relationship to successful aging over 18 years of follow-up in CHS. We will also evaluate the relationship of cystatin-C to changes in aging risk factors (inflammatory, other vascular and body compositional risk factors), subclinical disease (cardiovascular, cerebrovascular and musculoskeletal), clinical disease (cardiovascular, cerebrovascular and musculoskeletal) and rates of decline in physical and cognitive function. We hypothesize that kidney function will be a major and independent determinant of aging success across the spectrum from well-preserved (low cystatin-C) to average (medium cystatin-C) to poor kidney function (high cystatin-C). Our specific aims are as follows: To evaluate the relationship of serial measurements of kidney function, as determined by cystatin-C, to maintenance of successful aging; to evaluate the relationship between serial measurements of cystatin-C with longitudinal changes in risk factors for unsuccessful aging; to evaluate the relationship between serial measurements of cystatin-C with longitudinal changes in subclinical disease; to evaluate the relationship between serial measurements of cystatin-C with clinical disease in follow-up. Statistical analyses reveal adequate power for each of the aims. The Renal Working Group includes a group of both senior as well as new investigators to CHS, and disciplines including cardiovascular, geriatric and kidney-related epidemiology. The group has played an important role in advancing research in kidney disease. The team is therefore capable of successfully completing the aims within the time frame proposed. Relevance to public health: Abnormalities in kidney function are frequently found in older adults. We have a novel test, cystatin-C, that accurately assesses level of kidney function. The goal of this application is to evaluate whether cystatin-C is associated with complications of aging. If so, preservation of kidney function may be key to successful aging.